Alpinetin inhibits proliferation and migration of ovarian cancer cells via suppression of STAT3 signaling

Abstract

Natural bioactive components are increasingly being applied in cancer research. Alpinetin is a type of natural flavonoid primarily derived from Alpinia katsumadai Hayata, which exhibits anti‑bacterial and anti‑inflammatory properties. Therefore, it may possess anticancer potential and be employed therapeutically for different diseases. The aim of the present study was to investigate the anticancer effects of alpinetin on the SKOV3 ovarian cancer cell line. The effect of alpinetin treatment on SKOV3 cell proliferation, apoptosis, spheroid and colony formation were measured using Cell Counting kit‑8, cell apoptosis, 3D spheroid and colony formation assays, respectively. Analysis of the cell cycle was performed using flow cytometry. Western blot analysis was used to determine the protein expression levels of B‑cell lymphoma (Bcl)‑2, Bcl‑2‑associated X protein, cleaved caspase‑3, cleaved poly (ADP‑ribose) polymerase (PARP), cyclin D1, cyclin‑dependent kinase (CDK) 4, CDK6, signal transducer and activator of transcription (STAT) 3, phosphorylated (p)‑STAT3, c‑myc, survivin, tissue inhibitor of metalloproteinase (TIMP)‑1, TIMP‑2, matrix metalloproteinase (MMP)‑2 and MMP‑9. In addition, a wound healing assay was used to determine cancer cell migration. The results revealed alpinetin suppressed cell viability and induced apoptosis of SKOV3 cells in a dose‑ and time‑dependent manner, and cells were arrested in the G1 phase. Alpinetin treatment upregulated protein expression levels of Bax, cleaved caspase‑3 and PARP, and downregulated protein expression levels of Bcl‑2, cyclin D1, CDK4 and CDK6. Alpinetin also inhibited cell migration, through increased protein expression levels of TIMP‑1 and TIMP‑2, and decreased protein expression levels of MMP‑2 and MMP‑9. Alpinetin also significantly suppressed colony and spheroid formation by SKOV3 cells. In addition, the STAT3 pathway was suppressed as demonstrated by downregulation of p‑STAT3 and reduced expression of downstream factors, including c‑myc and survivin. Overall, these results indicated that alpinetin may have anticancer effects on human ovarian cancer by inhibiting the STAT3 signaling pathway.

Metabolic Profiling of Alpinetin in Rat Plasma, Urine, Bile and Feces after Intragastric Administration

“…It is considered as the primary active ingredient of Zingiberaceae ( Alpinia katsumadai Hayata) [2]. Modern pharmacological research shows a series of pharmacological activities that are involved in alpinetin, including anti-inflammatory [3,4,5,6], anti-cancer [7,8,9,10], anti-oxidant effects [11]. Alpinetin was found to improve the sensitivity of drug-resistant lung cancer cells to cis-diammined dichloridoplatium [10], which may be used as a potential drug for combination therapy.…”

Isolinderalactone Induces Cell Death via Mitochondrial Superoxide- and STAT3-Mediated Pathways in Human Ovarian Cancer Cells

“…The generation of mtSOs and reduced expression of anti-apoptotic Bcl-2 family proteins by ILL resulted in the loss of MMP ( Figure 3 C). Several previous reports suggested that STAT3 participates in the regulation of the anti-apoptotic Bcl-2 family proteins in human OC cells [ 35 , 36 ]. In the present study, ILL treatment dramatically reduced the expression and phosphorylation of STAT3, as well as the expression levels of surviving, in a time- and dose-dependent manner, while ILL decreased expression of JAK2 only in SKOV-3 cells and inhibited phosphorylation of JAK2 at the highest dose ( Figure 4 A,B).…”

Flavonoids against the Warburg phenotype—concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism

“…Therapeutic strategies focused on specific cancer metabolism linked to the Warburg effect are currently under extensive consideration [174,175]. To this end, naturally occurring bioactive compounds of plants demonstrate clinically relevant beneficial effects against cancer development and progression [223][224][225][226][227][228][229][230]. The combination use of phytochemicals and chemotherapeutical drugs may represent an optimal modality for anticancer therapy [231].…”